Cyclic strain of poly (methyl methacrylate) surfaces triggered the pathogenicity of Candida albicans.

Candida albicans is an opportunistic yeast and the primary etiological factor in oral candidiasis and denture stomatitis. The pathogenesis of C. albicans could be triggered by several variables, including environmental, nutritional, and biomaterial surface cues. Specifically, biomaterial interactions are driven by different surface properties, including wettability, stiffness, and roughness. Dental biomaterials experience repetitive (cyclic) stresses from chewing and biomechanical movements. Pathogenic biofilms are formed over these biomaterial surfaces under cyclic strain. This study investigated the effect of the cyclic strain (deformation) of biomaterial surfaces on the virulence of Candida albicans. Candida biofilms were grown over Poly (methyl methacrylate) (PMMA) surfaces subjected to static (no strain) and cyclic strain with different levels (ε˜x=0.1 and 0.2%). To evaluate the biomaterial-biofilm interactions, the biofilm characteristics, yeast-to-hyphae transition, and the expression of virulent genes were measured. Results showed the biofilm biomass and metabolic activity to be significantly higher when Candida adhered to surfaces subjected to cyclic strain compared to static surfaces. Examination of the yeast-to-hyphae transition showed pseudo-hyphae cells (pathogenic) in cyclically strained biomaterial surfaces, whereas static surfaces showed spherical yeast cells (commensal). RNA sequencing was used to determine and compare the transcriptome profiles of cyclically strained and static surfaces. Genes and transcription factors associated with cell adhesion (CSH1, PGA10, and RBT5), biofilm formation (EFG1), and secretion of extracellular matrix (ECM) (CRH1, ADH5, GCA1, and GCA2) were significantly upregulated in the cyclically strained biomaterial surfaces compared to static ones. Genes and transcription factors associated with virulence (UME6 and HGC1) and the secretion of extracellular enzymes (LIP, PLB, and SAP families) were also significantly upregulated in the cyclically strained biomaterial surfaces compared to static. For the first time, this study reveals a biomaterial surface factor triggering the pathogenesis of Candida albicans, which is essential for understanding, controlling, and preventing oral infections. STATEMENT OF SIGNIFICANCE: Fungal infections produced by Candida albicans are a significant contributor to various health conditions. Candida becomes pathogenic when certain environmental conditions change, including temperature, pH, nutrients, and CO2 levels. In addition, surface properties, including wettability, stiffness, and roughness, drive the interactions between Candida and biomaterials. Clinically, Candida adheres to biomaterials that are under repetitive deformation due to body movements. In this work, we revealed that when Candida adhered to biomaterial surfaces subjected to repetitive deformation, the microorganism becomes pathogenic by increasing the formation of biofilms and the expression of virulent factors related to hyphae formation and secretion of enzymes. Findings from this work could aid the development of new strategies for treating fungal infections in medical devices or implanted biomaterials.

Antifungal Effect of Piezoelectric Charges on PMMA Dentures.

Candida-associated denture stomatitis is a recurring disease affecting up to 67% of denture wearers. Poly(methyl methacrylate) (PMMA) remains the main material employed in the fabrication of dentures due to its desirable physical, mechanical, and aesthetic properties. However, the improvement of its antimicrobial properties remains a challenge. To address this need, we developed PMMA composite filled with piezoelectric nanoparticles of barium titanate (BaTiO3) for therapeutic effects. Candida albicans biofilms were cultivated on the surface of the composites under continuous cyclic mechanical loading to activate the piezoelectric charges and to resemble mastication patterns. The interactions between biofilms and biomaterials were evaluated by measuring the biofilm biomass, metabolic activity, and the number of viable cells. To explore the antifungal mechanisms, changes in the expression of genes encoding adhesins and superoxide dismutase were assessed using reverse transcription-polymerase chain reaction. With the addition of piezoelectric nanoparticles, we observed a significant reduction in the biofilm formation and interference in the yeast-to-hyphae transition compared to the standard PMMA. Moreover, we observed that the cyclic deformation of biomaterial surfaces without antifungal agents produced increased biomass, metabolic activity, and a number of viable cells compared to the static/no-deformed surfaces. Cyclic deformation appears to be a novel mechanobiological signal that enables pathogenicity and virulence of C. albicans cells with increased expression of the yeast-to-hyphae transition genes. The outcome of this study opens new opportunities for the design of antifungal dentures for improved clinical service and reduced need for cleaning methods.